Untitled

Abstract

IDE is the major enzyme which degrades insulin in enterocytes.

Immunohistochemical Localization of Insulin-Degrading Enzyme Along the Rat Intestine, in the Human Colon Adenocarcinoma Cell Line (Caco-2), and in Human Ileum

“…Western BlottingsThe cytosolic fractions from rat and human intestines and Caco-2 cells were prepared, and Western blots were performed as published previously. 16,18,19 Results and Discussion IDE is present in rat hepatocytes, so the rat liver was used as a positive control. As shown in Figure 1, the immunostain- ing of IDE was heterogeneous throughout central and portal vein regions, weaker in the central regions (C), but more intense in the portal regions (P).…”

“…Because insulin is reportedly transported transcellularly through the intestinal epithelium of rats, 14,15 the importance of intracellular metabolism in limiting the oral absorption of insulin can not be over-emphasized. Previous studies from our laboratory have shown that the majority of insulindegrading activity (IDA) is from the cytosolic fractions of rat 16,17 and human 18 enterocytes and human adenocarcinoma (Caco-2) cells. 19 The cytosolic IDA of these cells all exhibit a K m in the range 14-92 nM, which is comparable to that of IDE.…”

Metal ions affect insulin-degrading enzyme activity

“…It is also interesting to outline that if we compare these parameters with those obtained for the amyloid peptides Aβ [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16] and Aβ [16][17][18][19][20][21][22][23][24][25][26][27][28] several similarities and some differences emerge [54]. In particular, the overall proteolytic activity toward the main cleavage sites (i.e., Phe 24 [16][17][18][19][20][21][22][23][24][25][26][27][28] ) is somewhat higher in the case of the B20-30 peptide due to a slightly more efficient cleavage rate-limiting step (see Table 2), whereas the substrate affinity of B20-30 appears intermediate between that of Aβ [1][2][3]…”

“…Insulin degradation plays a major role in controlling insulin activity and most evidence supports IDE (insulin-degrading enzyme) as the primary degradative agent [1,2]. IDE is a zinc metalloprotease containing an unusual inverse zinc-binding site, HxxEH, that is involved in catalysis [3].…”

Oral Protein and Peptide Drug Delivery

“…30 Inhibitors of insulin-degrading enzyme include 1,10 phenanthroline, p-choromeribenzoate, 31 and bacitracin. 32 Ziv et al 33 reported the use of a combination of an enhancer, sodium cholate, and a protease inhibitor to achieve a 10% increase in rat intestinal insulin absorption.…”